Hypoparathyroidism for USMLE Step 3
Hypoparathyroidism for the USMLE Step 3 Exam
- Pathophysiology
- Hypoparathyroidism is characterized by insufficient secretion or action of parathyroid hormone (PTH), leading to hypocalcemia and hyperphosphatemia. PTH normally increases serum calcium by stimulating bone resorption, enhancing renal calcium reabsorption, and promoting intestinal calcium absorption through vitamin D activation.
- Primary Mechanisms:
- Reduced PTH Secretion: Most commonly due to damage to or destruction of the parathyroid glands.
- Pseudohypoparathyroidism: PTH secretion is normal or elevated, but the target tissues are resistant to its effects.
- Etiology
- Post-Surgical Hypoparathyroidism: The most common cause, usually following thyroidectomy, parathyroidectomy, or neck surgeries.
- Autoimmune Hypoparathyroidism: Autoimmune destruction of the parathyroid glands, often seen with polyglandular autoimmune syndromes.
- Congenital Causes:
- DiGeorge Syndrome: Congenital absence or underdevelopment of the parathyroid glands.
- Familial Hypoparathyroidism: Genetic mutations affecting PTH production or function.
- Radiation-Induced Hypoparathyroidism: Damage to parathyroid glands from radiation therapy for head and neck cancers.
- Magnesium Abnormalities: Severe hypomagnesemia impairs PTH secretion and action.
- Clinical Features
- Neuromuscular Symptoms:
- Tetany: Involuntary muscle cramps and spasms, especially in the hands and face.
- Chvostek’s Sign: Twitching of the facial muscles when the facial nerve is tapped.
- Trousseau’s Sign: Carpal spasm induced by inflating a blood pressure cuff above systolic pressure.
- Paresthesia: Tingling or numbness around the mouth, fingers, and toes.
- Seizures: Hypocalcemia lowers the seizure threshold.
- Cardiovascular Symptoms:
- Prolonged QT Interval: Hypocalcemia can lead to QT prolongation, increasing the risk of arrhythmias.
- Hypotension: Due to impaired calcium-mediated smooth muscle contraction.
- Mental Status Changes:
- Irritability, anxiety, and confusion. Chronic hypocalcemia may lead to neuropsychiatric disturbances.
- Severe Hypocalcemia:
- Laryngospasm or bronchospasm may occur, leading to respiratory distress.
- Diagnosis
- Serum Calcium: Low total and ionized calcium levels.
- Serum Phosphate: Elevated due to reduced phosphate excretion in the absence of PTH.
- Serum PTH: Low or inappropriately normal in the setting of hypocalcemia.
- Serum Magnesium: Low magnesium can impair PTH secretion and action.
- ECG: May reveal a prolonged QT interval due to hypocalcemia.
- Vitamin D Levels: Should be checked to rule out vitamin D deficiency.
- Management
- Acute Hypocalcemia:
- Intravenous Calcium: Administered in symptomatic patients (e.g., tetany, seizures, cardiac arrhythmias) as calcium gluconate.
- Monitoring: Continuous ECG monitoring is required due to the risk of arrhythmias during calcium administration.
- Chronic Hypocalcemia:
- Oral Calcium Supplements: Calcium carbonate or calcium citrate is used for long-term management to maintain calcium in the low-normal range.
- Vitamin D Supplementation:
- Calcitriol (Active Vitamin D): Essential in hypoparathyroidism to enhance intestinal calcium absorption.
- Thiazide Diuretics: May be used to reduce urinary calcium excretion, thus lowering the risk of nephrolithiasis.
- Magnesium Supplementation: Hypomagnesemia must be corrected to restore PTH secretion and function.
- Recombinant Human PTH (rhPTH):
- Natpara (rhPTH 1-84): Used for patients with refractory hypocalcemia who are dependent on high doses of calcium and vitamin D.
- Complications
- Hypocalcemic Crisis: Life-threatening tetany, laryngospasm, or arrhythmias due to severe hypocalcemia, requiring emergency IV calcium administration.
- Nephrocalcinosis: Chronic calcium and vitamin D therapy can lead to calcium deposition in the kidneys.
- Ectopic Calcifications: Prolonged hypoparathyroidism can result in calcium deposition in soft tissues, including the basal ganglia, leading to movement disorders.
Key Points
- Hypoparathyroidism is most often caused by surgical removal or damage to the parathyroid glands, leading to hypocalcemia and hyperphosphatemia.
- Symptoms include tetany, paresthesia, prolonged QT interval, and mental status changes. Severe hypocalcemia can lead to life-threatening complications such as laryngospasm and cardiac arrhythmias.
- Diagnosis is based on low serum calcium, elevated phosphate, and low PTH levels. Magnesium deficiency should be evaluated, as it can exacerbate hypocalcemia.
- Management includes acute IV calcium replacement for symptomatic hypocalcemia, with long-term treatment involving oral calcium, calcitriol, and magnesium supplementation. Recombinant PTH can be used for refractory cases.